Premium
Altered Pharmacokinetics of Indinavir by a Novel Nonnucleoside Reverse Transcriptase Inhibitor (HBY‐097): A Pharmacokinetic Evaluation in HIV‐Positive Patients
Author(s) -
Hayashi Sandra,
Jayesekera Deepthi,
Jayewardene Anura,
Shah Anita,
Thevanayagam Lourdes,
Aweeka Francesca
Publication year - 1999
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/00912709922011746
Subject(s) - pharmacokinetics , cmin , indinavir , cmax , zidovudine , pharmacology , reverse transcriptase inhibitor , area under the curve , chemistry , medicine , human immunodeficiency virus (hiv) , antiretroviral therapy , viral load , virology , viral disease
HBY‐097 (HBY), an investigational nonnucleoside reverse transcriptase inhibitor (NNRTI), and indinavir (IDV) share a common metabolic pathway, cytochrome P4503A4 (CYP3A4), and may clinically be used together as well as with zidovudine (ZDV). Thus, the potential pharmacokinetic (PK) interaction between these drugs was evaluated. HBY (500 mg Q8H), IDV (800 mg Q8H), and ZDV (200 mg Q8H) were given to 8 HIV‐infected subjects. Serial plasma samples were collected at baseline (ZDV and IDV alone) and day 11 (all 3drugs) to determine PK parameters using noncompartmental analysis. PK parameters for ZDV in the presence and absence of HBY were not appreciably different. However, both the maximum (C max ) and minimum (C min ) concentrations of IDV were significantly reduced, from a mean of 7514 ⌖ 1636 and 146 ⌖ 81 mcg/L to 4725 ⌖ 2494 mcg/L and 54 ⌖ 24 mcg/L ( p < .05) after addition of HBY. Furthermore, apparent clearance (CL/F) of IDV before and after 11 days of concomitant HBY administration was significantly higher, from 0.69 ⌖ 0.14 to 1.94 ⌖ 0.63 L/h/kg ( p < .05) with an associated reduction in area under the curve (AUC 0–8 ) from 16,034 ⌖ 4903 to 6134 ⌖ 2701 mg/L/h ( p < .05). The increase in IDV CL/F is consistent with the observed metabolic induction effects of other NNRTIs. The results of this trial showed that HBY significantly alters the pharmacokinetic parameters of IDV at the dose studied .